Tools for Practice

#325 Topical Anal Fissure Treatments – getting to the bottom of it

How effective are topical treatments (calcium channel blockers, nitrates and vitamin E) in adults with chronic anal fissures?

Healing rates with topical nitroglycerin are ~60% compared to 40% on placebo at 8 weeks. Topical calcium channel blockers are at least as good, with a lower risk of headache (7% versus 56%). Based on 1 randomized, controlled trial (RCT), topical vitamin E may be superior to nitroglycerins (86% versus 66% healed at 8 weeks).

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  • Five systematic reviews of RCTs in last 10 years.1-5 Focusing on most recent. Adjunctive treatments usually unclear (often fiber or dietary advice). Healing mostly defined as determined on exam or patient reported.
  • Calcium channel blockers (example diltiazem 2% ointment):
    • Healing (4 RCTs, 372 patients):
      • At 6 weeks, 78% versus 42% (placebo), number needed to treat (NNT)=3 (calculated by PEER).1
      • Other systematic reviews found similar.2,3
  • Nitroglycerins (example nitroglycerin 0.2-0.4% ointment):
    • Healing (17 RCTs, 1063 patients):
      • At 8 weeks,1 63% versus 38% (placebo), NNT=4.
      • Other systematic reviews found efficacy ~50% versus 35% (placebo).2,3
  • Calcium channel blockers versus nitroglycerins:
    • Healing (11 RCTs, 770 patients):
      • At 8 weeks, 79% versus 65% nitroglycerin.1
      • Similar in other systematic reviews,3-5 but only statistically different in 1 review.3
    • Headache (10 RCTs, 590 patients):
      • 7% versus 56% nitroglycerin.1
  • Limitations:
    • Many systematic reviews included pediatrics, did not include all RCTs and had suboptimal statistical analysis; many RCTs unblinded and considered high risk of bias.
  • Vitamin E:
    • 1 RCT, 160 patients, topical vitamin E or topical nitroglycerin twice daily.6 At 8 weeks:
      • Healing: 86% versus 66% nitroglycerin, NNT=5.
      • Stopping due to headache: 0 versus 18% nitroglycerin.
    • Limitations: Patients unblinded, nitroglycerin possibly underdosed, unknown IU/g of vitamin E.
  • Most fissures are at the midline. Other locations may indicate secondary cause (example Crohn’s disease) and should be investigated.7
  • Guidelines recommend topical calcium channel blockers or topical nitroglycerins.8,9
    • Botox and surgery are options for treatment failure, but fecal incontinence possible.9
  • Cost (~8 weeks):
    • Compounded topical calcium channel blocker/nitroglycerin: ~$60/30g.10
    • Commercially available vitamin E ointment = ~$10/50g.11

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  • Adrienne J Lindblad BSP ACPR PharmD
  • Callie Fagan BSP
  • Michael R Kolber MD CCFP MSc

1. Jin JZ, Hardy MO, Unasa H, et al. Int J Colorectal Dis. 2022; 37:1-15.

2. Nelson RL, Thomas K, Morgan J, et al. Cochrane Database System Rev. 2012; 2:CD003431.

3. Nelson RL, Manuel D, Gumienny C, et al. Tech Coloproctol. 2017; 21:605-25.

4. Nevins EJ, Kanakala V. Turk J Surg. 2020; 36(4):347-52.

5. Sajid MS, Whitehouse PA, Sains P, et al. Colorectal Dis. 2012; 15:19-26.

6. Ruiz-Tovar, J, Llavero C. Dis Colon Rectum. 2022; 65:406-12.

7. Dykstra MA, Buie WD. CMAJ. 2019 July; 191:E737.

8. Stewart DB Sr, Gaertner W, Glasgow S, et al. Dis Colon Rectum. 2017; 60(1):7-14.

9. Wald A, Bharucha AE, Limketkai B, et al. Am J Gastroenterol. 2021; 116(10):1987-2008.

10. Personal communication: Stacy Jardine, clinical pharmacist at Peace River Value Drug Mart, Peace River, Alberta. October 4, 2022.

11. Webber Vitamin E First Aid Ointment on Available at: Accessed October 7, 2022.

Authors do not have any conflicts of interest to declare.